Alagille syndrome caused by NOTCH2 mutation presented atypical pathological changes

Area of Science:

• Genetics
• Rare Diseases
• Pediatric Hepatology

Background:

• Alagille syndrome (ALGS) is a rare genetic disorder affecting multiple systems.
• Mutations in JAG1 are common, but NOTCH2 mutations are infrequently identified in ALGS patients.
• Clinical and pathological features of ALGS associated with NOTCH2 mutations are not well-characterized.

Observation:

• A 16-year-old female presented with recurrent jaundice and abnormal liver function since infancy.
• She exhibited characteristic Alagille syndrome facial features and butterfly vertebrae.
• Genetic analysis revealed a pathogenic heterozygous variant (c.5857 C>T) in the NOTCH2 gene.

Findings:

• The patient's liver biopsy showed a disordered liver structure with cholestasis and portal fibrosis.
• This liver pathology differs from the typical bile duct paucity observed in JAG1-deficient ALGS.
• Diagnosis of Alagille syndrome was confirmed.

Implications:

• This case underscores the importance of considering NOTCH2 mutations in Alagille syndrome.
• It highlights distinct clinical and pathological presentations in NOTCH2-mutated ALGS.
• Further research into NOTCH2-related ALGS is warranted to understand its unique characteristics.